Inhibition of inducible nitric oxide synthase exacerbates chronic cerebraltoxoplasmosis in Toxoplasma gondii-susceptible C57BL/6 mice but does not reactivate the latent disease in T-gondii-resistant BALB/c mice

Infection of C57BL/6 mice with Toxoplasma gondii leads to progressive and u ltimately fatal chronic Toxoplasma encephalitis (TE), Genetic deletion or i nhibition of inducible nitric oxide synthase (iNOS) from the beginning of i nfection increased the number of T. gondii cysts in the brain and markedly reduced the time-to-death in this mouse strain. In the present study, we ad dressed whether iNOS also contributes to the control of intracerebral paras ites in a clinically stable latent infection that develops in T. gondii-res istant BALB/c mice after resolution of the acute phase of TE, iNOS was expr essed in the inflammatory cerebral infiltrates of latently infected BALB/c mice, but the number of iNOS(+) cells was significantly lower than in the b rains of chronically infected T. gondii-susceptible C57BL/6 mice. In BALB/c mice,vith latent TE (>30 days of infect-ion), treatment with the MOS inhib itors L-N-6-iminoethyl-lysine or L-nitroarginine-methylester for less than or equal to 40 days did not result in an increase of the intracerebral para sitic load and a reactivation of the disease, despite the presence of iNOS- suppressive inhibitor levels in the brain, However, L-nitroarginine-methyle ster treatment had remarkably toxic effects and induced a severe wasting sy ndrome with high mortality, In contrast to BALB/c mice, L-N-6-iminoethyl-ly sine treatment rapidly exacerbated the already established chronic TE of C5 7BL/6 mice, Thus, the containment of latent toxoplasms in T,gondii-resistan t BALB/c mice is independent of iNOS, whereas the temporary control of intr acerebral parasites in T. gondii-susceptible C57BL/6 mice with chronic TE r equires iNOS activity.